High-throughput cancer hypothesis testing with an integrated PhysiCell-EMEWS workflow

Background Cancer is a complex, multiscale dynamical system, with interactions between tumor cells and non-cancerous host systems. Therapies act on this combined cancer-host system, sometimes with unexpected results. Systematic investigation of mechanistic computational models can augment traditional laboratory and clinical studies, helping identify the factors driving a treatment’s success or failure. However, given the uncertainties regarding the underlying biology, these multiscale computational models can take many potential forms, in addition to encompassing high-dimensional parameter spaces. Therefore, the exploration of these models is computationally challenging. We propose that integrating two existing technologies—one to aid the construction of multiscale agent-based models, the other developed to enhance model exploration and optimization—can provide a computational means for high-throughput hypothesis testing, and eventually, optimization. Results In this paper, we introduce a high throughput computing (HTC) framework that integrates a mechanistic 3-D multicellular simulator (PhysiCell) with an extreme-scale model exploration platform (EMEWS) to investigate high-dimensional parameter spaces. We show early results in applying PhysiCell-EMEWS to 3-D cancer immunotherapy and show insights on therapeutic failure. We describe a generalized PhysiCell-EMEWS workflow for high-throughput cancer hypothesis testing, where hundreds or thousands of mechanistic simulations are compared against data-driven error metrics to perform hypothesis optimization. Conclusions While key notational and computational challenges remain, mechanistic agent-based models and high-throughput model exploration environments can be combined to systematically and rapidly explore key problems in cancer. These high-throughput computational experiments can improve our understanding of the underlying biology, drive future experiments, and ultimately inform clinical practice.


Publication Date:
Dec 21 2018
Date Submitted:
Jun 28 2019
Pagination:
82-97
Citation:
BMC Bioinformatics
19
Suppl 18
External Resources:




 Record created 2019-06-28, last modified 2019-07-24


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